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Context: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. Methods: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. Results: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. Conclusion: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy., SCOPUS: re.j, info:eu-repo/semantics/published

Background Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals.Methods We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the nonpregnancy reference intervals included an absolute modification (per .1 mU/L TSH or 1 pmol/L free T4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 and 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity, and positive predictive value (PPV) of these methodologies with population-based trimester-specific reference intervals.Results The final study population comprised 52 496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity, .70, CI, 0.47-0.86; PPV, 0.64, CI, 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity, 0.91; CI, 0.67-0.98; PPV, 0.71, CI, 0.58-0.80). Absolute and fixed modifications yielded similar results. CIs were wide, limiting generalizability.Conclusion We could not identify modifications of nonpregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned toward studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.

Context: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. Methods: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. Results: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. Conclusion: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (r, Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk f

CONTEXT: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations.METHODS: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines.RESULTS: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches.CONCLUSION: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Objectives: High plasma copper (Cu) and low zinc (Zn) levels have been associated with depression. However, most studies used low sample sizes and a cross-sectional design, and perinatal data are scarce. We investigated the possible association between pregnancy-specific psychological distress and the plasma CuZn ratio using a prospective design. Methods: Pregnancy-specific distress symptoms were assessed at each trimester by means of the Tilburg Pregnancy Distress Scale, negative affect subscale, in 2036 pregnant women. Cu and Zn were assessed at 12 wk of gestation in plasma samples by inductively coupled plasma mass spectrometry. Growth mixture modeling determined trajectories of women's pregnancy-specific negative affect (P-NA) symptoms, which were entered in a multiple logistic regression analysis as dependent variable and the CuZn ratio as independent variable. Results: Two P-NA symptom classes were found: 1) persistently low (n = 1820) and 2) persistently high (n = 216). A higher CuZn ratio was independently associated with persistently high P-NA symptom scores (odds ratio = 1.52; 95% confidence interval, 1.13–2.04) after adjustment for confounders. A sensitivity analysis was performed excluding all women with high P-NA scores at 12 wk (>1 SD above the mean P-NA score). In the 1719 remaining women, a higher CuZn ratio significantly predicted the development of increasing P-NA symptom scores after adjustment for confounders (odds ratio = 1.40; 95% confidence interval, 1.04–1.95). Conclusions: A higher CuZn plasma ratio is an independent determinant of developing pregnancy-specific distress symptoms throughout pregnancy, suggesting that micronutrients could be used as novel biomarkers for psychological distress research of perinatal mood disorders.

Synopsis Results of a large prospective pregnancy cohort in the Netherlands show no association of severe acute respiratory syndrome coronavirus 2 infection prior to 28 weeks of gestation with adverse obstetric outcomes.

Results of a large prospective pregnancy cohort in the Netherlands show no association of severe acute respiratory syndrome coronavirus 2 infection prior to 28 weeks of gestation with adverse obstetric outcomes.

A comment on the recently published letter by Grogan and Srinivasan: The effect of antenatal depressive and anxious symptoms on the rate of physiological births.

OBJECTIVE: Pregnancy-induced hypertension (PIH) is associated with serious complications in both the mother and the unborn child. We examined the possible association between trajectories of maternal psychological distress symptoms and PIH separately in primiparous and multiparous women.METHODS: Pregnancy-specific negative affect (P-NA) and depressive symptoms were assessed prospectively at each trimester using the Tilburg Pregnancy Distress Scale pregnancy negative affect subscale (P-NA) and the Edinburgh Depression Scale (EDS). Data on PIH were collected from medical records. Growth mixture modeling analysis was used to identify trajectories of P-NA and EDS. The independent role of P-NA and EDS symptom trajectories on developing PIH was examined using multivariate logistic regression models.RESULTS: One hundred (7.6%) women developed PIH and were compared with 1219 women without hypertension or other complications during pregnancy. Three P-NA trajectories were identified: low stable (reference group; 90%), decreasing (5.2%), and increasing (4.8%). The latter two classes showed persistently and significantly higher P-NA symptoms during pregnancy compared with the reference group. In multiparous women, high P-NA scores (belonging to classes 2 and 3) were related to PIH (odds ratio [OR] = 6.91, 95% confidence interval [CI] = 2.26-21.2), independent of body mass index (OR = 1.17, 95% CI = 1.06-1.27) and previous PIH (OR = 14.82, 95% CI = 6.01-32.7). No associations between P-NA and PIH were found in primiparous women. EDS trajectories were not related to PIH in both primiparous and multiparous women.CONCLUSIONS: In multiparous women, persistently high levels of P-NA symptoms but not depressive symptoms were independently associated with development of PIH.

Background: Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia. Methods: In this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585. Findings: We identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85·6%) women had sufficient data (TSH and FT4 concentrations and TPO antibody status) to be classified according to their thyroid function

Background: Current knowledge regarding differences in verbal intelligence scores (VIQ) and performance intelligence scores (PIQ) in preterm born children is limited. As early motor performance may be essential for developing later visual-perceptual and visual-motor skills, early motor performance may be associated with PIQ. Aims: To evaluate whether in preterm born children motor performance at two years was associated with PIQ at eight years. Methods: Single-centre cohort study including 88 children born <30 weeks' gestation between 2007 and 2011, who completed the Bayley Scales of Infant and Toddler Development-III (BSID-III) at two years and the Wechsler Intelligence Scale for Children-III-NL (WISC-III-NL) at eight years. Outcome measurements (mean (SD)) were gross and fine motor performance based on the BSID-III, and PIQ and VIQ based on the WISC-III-NL. Linear regression analysis was performed to evaluate the association between motor performance at two years and PIQ at eight years. Results: At two years, mean BSID-III gross motor scaled score was 9.0 (SD 3.0) and fine motor score was 11.5 (SD 2.3). At eight years, mean PIQ was 94.9 (SD 13.5) and mean VIQ 101.8 (SD 13.7). A one-point increase in fine motor scaled score was associated with 1.7 points (95% CI 0.5–2.8) increase in PIQ. Gross motor scaled score was not associated with PIQ. Conclusions: Fine motor performance in toddlerhood was related to PIQ at school age, with lower scores indicating a lower PIQ. Early assessment of fine motor performance may be beneficial in identifying children at risk for lower performance intelligence.

CONTEXT: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. OBJECTIVE: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. METHODS: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. RESULTS: (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. CONCLUSION: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria.

Objective: Occurrence of psychological distress in hypertensive patients could have a negative synergistic effect on future cardiovascular events (CVEs). The aim of this study was to determine the association between anxiety or depressive symptoms in elderly hypertensive primary care patients and the development of new CVEs and allcause mortality. Methods: A prospective cohort study was conducted in five Dutch general practices between June 2010 and January 2012. Patients with primary care managed hypertension, aged 60-85 years, were included and completed the GAD-7 and PHQ-9, measuring anxiety and depressive symptoms respectively. The incidence of new CVEs (coronary event, cerebrovascular disease, atrial fibrillation and heart failure) and all-cause mortality at 8 years' follow-up was recorded by data extraction of the digital information systems. Results: Among the 555 included participants (mean age 70 +/- 6.6 years; 56% female), 29 (5.2%) had a new coronary event, 42 (7.6%) a cerebrovascular disease, 57 (10.3%) atrial fibrillation, 22 (4%) heart failure and 68 (12.3%) died. Elevated anxiety and depression scores increased the risk of a coronary event independently and significantly by 12% (HR 1.12; 95% CI [1.04-1.22], p = 0.005) and 18% (HR 1.18; 95% CI [1.08-1.28], p < 0.0001), respectively, adjusted for relevant (Framingham) baseline covariates. No associations were found with regard to other CVEs and all-cause mortality. Conclusion: In a random sample of elderly primary care hypertension patients there was a significant association between psychological distress and the occurrence of new coronary events after 8 years' follow-up but not with other CVEs and all-cause mortality.

Objectives: Thyroid autoimmunity is common in pregnant women and associated with thyroid dysfunction and adverse obstetric outcomes. Most studies focus on thyroid peroxidase antibodies (TPOAbs) assessed by a negative-positive dichotomy and rarely take into account thyroglobulin antibodies (TgAbs). This study aimed at determining the association of TPOAbs and TgAbs, respectively, and interdependently, with maternal thyroid function.Methods: This was a meta-analysis of individual participant cross-sectional data from 20 cohorts in the Consortium on Thyroid and Pregnancy. Women with multiple pregnancy, pregnancy by assisted reproductive technology, history of thyroid disease, or use of thyroid interfering medication were excluded. Associations of (log2) TPOAbs and TgAbs (with/without mutual adjustment) with cohort-specific z-scores of (log2) thyrotropin (TSH), free triiodothyronine (fT3), total triiodothyronine (TT3), free thyroxine (fT4), total thyroxine (TT4), or triiodothyronine:thyroxine (T3:T4) ratio were evaluated in a linear mixed model.Results: In total, 51,138 women participated (51,094 had TPOAb-data and 27,874 had TgAb-data). Isolated TPOAb positivity was present in 4.1% [95% confidence interval, CI: 3.0 to 5.2], isolated TgAb positivity in 4.8% [CI: 2.9 to 6.6], and positivity for both antibodies in 4.7% [CI: 3.1 to 6.3]. Compared with antibody-negative women, TSH was higher in women with isolated TPOAb positivity (z-score increment 0.40, CI: 0.16 to 0.64) and TgAb positivity (0.21, CI: 0.10 to 0.32), but highest in those positive for both antibodies (0.54, CI: 0.36 to 0.71). There was a dose-response effect of higher TPOAb and TgAb concentrations with higher TSH (TSH z-score increment for TPOAbs 0.12, CI: 0.09 to 0.15, TgAbs 0.08, CI: 0.02 to 0.15). When adjusting analyses for the other antibody, only the association of TPOAbs remained statistically significant. A higher TPOAb concentration was associated with lower fT4 (p < 0.001) and higher T3:T4 r

Perinatal depression is common, affecting approximately 7–13% of women. Studies have shown an association between unplanned pregnancy and perinatal depressive symptoms, but many used a cross-sectional design and limited postnatal follow-up. The current study investigated the association of unplanned pregnancy with perinatal depressive symptoms using a longitudinal cohort study that followed women from the first trimester until 12 months postpartum. Pregnant women (N = 1928) provided demographic and clinical data and information about pregnancy intention at the first trimester. Depressive symptoms were assessed during each trimester of pregnancy and five times postpartum using the Edinburgh Postnatal Depression Scale (EPDS) until 12 months postpartum. Mixed model analyses were used to investigate the association between an unplanned pregnancy and the level of depressive symptoms. Women with an unplanned pregnancy (N = 111, 5.8%) reported persistently higher levels of depressive symptoms during the entire perinatal period compared to women with a planned pregnancy, after adjustment for confounders (p < 0.001). However, the course of depressive symptom scores over time in women with an unplanned pregnancy was similar to that of women with a planned pregnancy. Lower age (p = 0.006), unemployment (p = 0.004), and history of depression (p < 0.001) were significantly associated with higher levels of perinatal depressive symptoms. An unplanned pregnancy may have a long-lasting negative impact on a woman’s perinatal mental health. Therefore, women with an unplanned pregnancy may benefit from systematic follow-up during the perinatal period with contingent mental health support.

Pregnant women may be specifically prone to experience pregnancy-specific distress, which has been associated with adverse maternal, pregnancy and child outcomes. Accurately identifying pregnancy-specific distress is thus crucial. The Tilburg Pregnancy Distress Scale (TPDS) - translated into many different languages - was previously developed to measure pregnancy-specific distress, resulting in a 16-item screening scale with a partner involvement dimension (PI) and a negative affect dimension (NA). A critical evaluation of the psychometric properties of the TPDS-NA items and feedback from pregnant women over the last decade has led to the need to revise the TPDS. Therefore, in the current study, we describe the procedure for revision and evaluate the psychometric properties of the revised TPDS (TPDS-R). More specifically, we describe the revision of the TPDS-R-PI (4 items) and the TPDS-R-NA (10 items: five-item pregnancy and five-item childbirth subcomponent). A sample of 1081 pregnant women participating in the Brabant Study completed the TPDS-R at 12, 20 and 28 weeks of pregnancy. An exploratory factor analysis and confirmatory factor analysis, descriptive statistics and repeated measures ANOVA demonstrated good test-retest reliability, concurrent validity, internal consistency, and construct validity of the TPDS-R. The TPDS-R provides a robust screening tool to accurately identify pregnant women at risk of pregnancy-specific distress.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic elevated the risk for mental health problems in pregnant women, thereby increasing the risk for long-term negative consequences for mother and child well-being. There was an immediate need for easily accessible interventions for pregnant women experiencing elevated levels of pandemic related stress.Methods: A three-session intervention "Online Communities" (OC) was developed at the beginning of the Dutch lockdown, and implemented by a team of midwives and psychologists specialized in Infant Mental Health. Pretest (N = 34) and posttest (N = 17) measurements of depressive symptoms, worries about COVID-19 and worries in general, and mother-to-infant bonding were administered, as well as a posttest evaluation.Results: At pretest, the OC group was compared to two reference groups of pregnant women from an ongoing pregnancy cohort study: a COVID-19 (N = 209) and pre-COVID-19 reference group (N = 297). OC participants had significantly more depressive symptoms than both reference groups, and less positive feelings of bonding than the COVID-19 but not the pre-COVID-19 reference group. Compared to pretest, significant decreases in depressive symptoms (with significantly less participants scoring above cut-off) and worries about COVID-19 (large effect sizes) and worries in general (moderate to large effect size) were found at posttest for the OC participants. No significant improvement was found in bonding. Participants rated the intervention positively.Conclusions: The current study provides initial evidence supporting the idea that OC is a promising and readily accessible intervention for pregnant women experiencing stress due to the COVID-19 pandemic, and possibly also applicable to other stressors.Trial registration: This intervention was registered in the Netherlands Trial Registration (registration number Trial NL8842 , registration date 18/08/2020).

OBJECTIVE: Pregnancy-induced hypertension (PIH) is associated with serious complications in both the mother and the unborn child. We examined the possible association between trajectories of maternal psychological distress symptoms and PIH separately in primiparous and multiparous women.METHODS: Pregnancy-specific negative affect (P-NA) and depressive symptoms were assessed prospectively at each trimester using the Tilburg Pregnancy Distress Scale pregnancy negative affect subscale (P-NA) and the Edinburgh Depression Scale (EDS). Data on PIH were collected from medical records. Growth mixture modeling analysis was used to identify trajectories of P-NA and EDS. The independent role of P-NA and EDS symptom trajectories on developing PIH was examined using multivariate logistic regression models.RESULTS: One hundred (7.6%) women developed PIH and were compared with 1219 women without hypertension or other complications during pregnancy. Three P-NA trajectories were identified: low stable (reference group; 90%), decreasing (5.2%), and increasing (4.8%). The latter two classes showed persistently and significantly higher P-NA symptoms during pregnancy compared with the reference group. In multiparous women, high P-NA scores (belonging to classes 2 and 3) were related to PIH (odds ratio [OR] = 6.91, 95% confidence interval [CI] = 2.26-21.2), independent of body mass index (OR = 1.17, 95% CI = 1.06-1.27) and previous PIH (OR = 14.82, 95% CI = 6.01-32.7). No associations between P-NA and PIH were found in primiparous women. EDS trajectories were not related to PIH in both primiparous and multiparous women.CONCLUSIONS: In multiparous women, persistently high levels of P-NA symptoms but not depressive symptoms were independently associated with development of PIH.

Objectives Mindful parenting (MP) interventions show promising results, but they mostly target parents (of children) with mental health problems. This study examined an online MP intervention for mothers with toddlers in a population-based sample. Aims were to assess acceptability and effectiveness of the intervention for mothers with and without parental stress, and examine their predetermined personal goals. Methods The study included 157 mothers with toddlers from the general population of whom 73 reported parental stress. The mothers participated in an 8-week online MP training. Questionnaires were completed at waitlist, pretest, posttest, and follow-up. Results Mothers rated the training positively, although only 23.1% completed the training. Personal goals were analyzed qualitatively, establishing four different themes: attention, well-being, patience, and balance. Significant improvements in personal goals posttest and follow-up were found (large and very large effect size, respectively). We found no significant improvements from waitlist to pretest for all outcome variables, except personal goals (medium effect size). Mixed-linear model analyses showed significant improvements posttest and follow-up as compared to pretest regarding Self-compassion, Parental over-reactivity and Symptoms of anxiety and depression (small to medium effect sizes). There was an effect at posttest for Parenting problems, and for Parental role restriction at follow-up (small effect sizes). Levels of parental stress and theme of personal goal did not influence the effectiveness of the intervention. Conclusions The current study provides initial evidence that an online MP training could be an easily accessible, inexpensive, and valuable intervention for parents without an indication for a therapist-assisted intervention. Trial Registration Dutch Trial Register (NTR7401)

Importance: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them. Objective: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information. Data Sources: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019. Study Selection: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization. Data Extraction and Synthesis: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression. Main Outcomes and Measures: Patient Health Questionnaire-9 (PHQ-9) scores. Results: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (P

Background Internet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom. Methods We did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683. Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD −1·83 [95% credible interval (CrI) −2·90 to −0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and au

Purpose: Offspring of mothers with a bipolar disorder are at high-risk for impaired developmental outcomes and psychopathology (e. g., mood, anxiety, sleep disorders) later in life. This increased risk of psychopathology is not only because of genetic vulnerability, but environmental factors may play an important role as well. The often long and debilitating mood episodes of mothers with bipolar disorder might hamper their qualities as a caregiver and may impact the child. We examined early mother-to-infant bonding 1 year postpartum in mothers with bipolar spectrum disorder as compared to mothers of the general population. The association between mother-to-infant bonding and the type of bipolar spectrum diagnosis (bipolar I, bipolar II, bipolar Not Otherwise Specified) as well as relapse within 12 months postpartum was also assessed. Methods: In total, 75 pregnant women with a bipolar spectrum disorder participated in the current study. The participants were included in a longitudinal cohort study of women with bipolar spectrum disorder and were prospectively followed from pregnancy until 1 year postpartum. Mother-to-infant bonding was assessed using the Pre- and Postnatal Bonding Scale. A longitudinal population-based cohort of 1,419 pregnant women served as the control group. Multiple linear regression analyses were used to assess the association between bipolar spectrum disorder and mother-to-infant bonding scores, controlling for several confounders. Results: Women with bipolar spectrum disorder perceived the bonding with their child as less positive compared to the control group. The type of bipolar spectrum disorder was not associated with poorer bonding scores. Relapse during the 1st year after delivery also did not affect bonding scores in women with bipolar spectrum disorder. Conclusions: Our findings could imply that women with bipolar spectrum disorder are more vulnerable to impairments in bonding due to the nature of their psychopathology, regardless